RENAL DENERAVTION IN HTN
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This document summarizes the Simplicity HTN-2 and Simplicity HTN-3 clinical trials that evaluated the effectiveness of renal denervation for treating resistant hypertension. The Simplicity HTN-2 trial found that renal denervation significantly reduced blood pressure in patients with resistant hypertension compared to a control group. However, the larger Simplicity HTN-3 trial, which was blinded and sham-controlled, did not find a significant reduction in blood pressure between the renal denervation and sham groups at 6 months.
RENAL DENERAVTION IN HTN
- 2. • Hypertension is defined as a usual office blood pressure of 140/90 mm Hg or higher
- 4. RESISTANT HYPERTENSION • refers to patients with blood pressures persistently >140/90 mmHg despite taking three or more antihypertensive agents, including a diuretic, in a reasonable combination and at full doses
- 5. RENAL DENERVATION • overactivity of the sympathetic nervous system contributes to hypertension,especially severe drug-resistant hypertension. • The targets of RDN are both the efferent postganglionic renal sympathetic nerves and the renal sensory (afferent) nerves
- 7. Hypertrophy Arrhythmia Oxygen Consumption Vasoconstriction Atherosclerosis Insulin Resistance Renal Sympathetic Activation: Afferent Nerves Kidney as Origin of Central Sympathetic Drive Renal Afferent Nerves ↑ Renin Release RAAS activation ↑ Sodium Retention ↓ Renal Blood Flow Sleep Disturbances 7
- 10. • 8-F femoral artery access, an 8-F guide catheter was positioned in the renal arteries, allowing delivery of a radiofrequency catheter into the renal arteries and circumferential application of radiofrequency energy • The catheter tip is steerable via a hand control and is connected to a console • Delivery of radiofrequency energy was monitored with a temperature and impedance sensor at the tip of the catheter such that unwanted tissue injury related to overheating was avoided
- 13. The simplicity HTN-2 Trial • Purpose: To demonstrate the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with uncontrolled hypertension. • Study design: Randomized, controlled clinical trial. • Patients: 106 patients randomized 1:1 to treatment with renal denervation vs. control. • Participating centres: 24 centers in Europe, Australia, & New Zealand.
- 14. The simplicity HTN-2 Trial Inclusion Criteria: -Office SBP ≥ 160 mmHg (≥ 150 mmHg with type II diabetes mellitus) -3+ more anti-HTN medications -Age 18-85 years Exclusion Criteria: -Significant renal artery abnormalities or prior renal artery intervention -eGFR < 45 mL/min/1.73m2 -Type 1 diabetes -Contraindication to MRI -Significant stenotic valvular heart disease -MI, unstable angina, or CVA in the preceding 6 months
- 15. Before randomisation and to assess eligibility: • Screening process required patients to record daily bd automated BP measurements and to document drug compliance • Renal artery anatomical screening, with renal duplex, CT, MRI or renal angiography to confirm anatomical eligibility. • Baseline creatinine, Cystatin • 24hr BP measurement.
- 19. Follow up • At 1, 3 and 6 months, with rpt creat, Cystatin C, BP • Office and home BP readings, average of 3. • Daily home BP and drug compliance prior to the 6 month FU. • At 6 months: 24hr BP monitor and renal imaging in the renal denervation group.
- 20. . 84% of RDN patients had ≥10 mmHg reduction in SBP . 10% of RDN patients had no reduction in SBP . p <0.001 for difference between RDN and Control
- 26. Adverse events • No significant change in renal function. • One renal artery dissection from injection of contrast into renal artery wall during dye angiography. • The lesion was stented without further consequences. Minor adverse events (n=52) •1 femoral artery pseudoaneurysm manual compression •1 post-procedural drop in BP resulting in a reduction in medication •1 urinary tract infection •1 prolonged hospitalization for evaluation of paraesthesias •1 back pain treated with pain medications & resolved after one month 6-month renal imaging (n=43) •No vascular abnormality at any RF treatment site •1 MRA indicates possible progression of a pre-existing stenosis unrelated to RF treatment (no further therapy)
- 27. Conclusions • Catheter-based renal denervation, done in a multicentre, randomised trial in patients with treatment-resistant essential hypertension, resulted in significant reductions in BP. • The technique was applied without major complications. • This therapeutic innovation, based on the described neural pathophysiology of essential hypertension, affirms the crucial relevance of renal nerves in the maintenance of BP in patients with hypertension. • Catheter-based renal denervation may be beneficial for patients with treatment-resistant essential hypertension.
- 28. Limitations • Non-blinded trial. • ?long-term benefit, ?evidence of reinnervation • Small number of patients. • Was the population truly treatment resistant? • Adjustments in medications, unclear effect on pill burden • Effect in patients with severe CKD.
- 30. • SYMPLICITY HTN-3 is the first prospective, multi-center, randomized, blinded, sham controlled study to evaluate both the safety and efficacy of percutaneous renal artery denervation in patients with severe treatment-resistant hypertension. • The trial included 535 patients enrolled by 88 participating US centers.
- 31. • The primary efficacy end point was the mean change in office systolic blood pressure from baseline to 6 months in the denervation group, as compared with the mean change in the sham control group, with a superiority margin of 5 mm Hg • a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure
- 32. • The primary safety end point was a composite of major adverse events, defined as death from any cause, endstage renal disease, an embolic event resulting in end-organ damage, renal-artery or other vascular complications, or hypertensive crisis within 30 days or new renal-artery stenosis of more than 70% within 6 months.
- 33. Key Inclusion Criteria • Age ≥18 and ≤80 years at time of randomization • Stable medication regimen including full tolerated doses of 3 or more antihypertensive medications of different classes, including a diuretic (with no changes for a minimum of 2 weeks prior to screening) and no expected changes for at least 6 months • Office SBP ≥160 mm Hg based on an average of 3 blood pressure readings measured at both an initial and a confirmatory screening visit • Written informed consent
- 34. Key Exclusion Criteria • ABPM 24 hour average SBP <135 mm Hg • eGFR of <45 mL/min/1.73 m2 • Main renal arteries <4 mm diameter or <20 mm treatable length • Multiple renal arteries where the main renal artery is estimated to supply <75% of the kidney • Renal artery stenosis >50% or aneurysm in either renal artery • History of prior renal artery intervention
- 41. • This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control.